Aim Fluorescence resonance energy transfer (FRET), in which light energy absorbed by a donor is transferred to a nearby acceptor, is a powerful tool for measuring changes in molecular distances. The efficiency of FRET falls off with the sixth power of the distance between the two molecules, making FRET very sensitive to changes in distance. However, FRET can measure distances effectively only in a narrow range of distances that are not always well suited to study intra-molecular movements in proteins. We are developing rapid high throughput methods that use transition metal ions (nickel and copper) as energy acceptors for small fluorescent donor dyes (bimane) to map the conformational rearrangements of engineered proteins. These transition metal ion FRET (tmFRET) fluorescent methods work over shorter distances than classical FRET, use smaller dyes with shorter linkers, and are not as sensitive to the orientation problems usually associated with other methods. In this work, we have used tmFRET to map 10 unique distances in the model protein Maltose Binding Protein (MBP) in both the ligand-bound (HOLO) and ligand-free (APO) state. We have mapped distances between two donor dyes (monobromo-bimane and fluorescein-5-maleimide) and the two acceptor metals (nickel and copper). This has given us a total of 40 independent distance measurements in MBP. When these distances were compared to the x-ray crystal structure of MBP our tmFRET distances match the x-ray crystal structure to within a few angstroms. Furthermore, tmFRET was able to accurately detect structural changes in the protein during ligand binding. With the above experimental data, we next tested if distances derived with tmFRET could be used to guide molecular dynamics simulations. In these tmFRET-constrained simulations, MBP was allowed to move from the ligand-bound state to the APO state. Without tmFRET-derived distance constraints, the simulations did find the APO conformation of MBP. Simulations that contained the tmFRET-derived distances rapidly adopted the APO state. We conclude that tmFRET can be used to drive the conformational folding of proteins structures to an accuracy of a few angstroms. We have continued to develop this method as applied to other proteins. We have explored new metals including zinc and cobalt for binding and fluorescence effects. We have additionally developed new structural models of the angstrom-scale architecture of these systems and how they can be used to map other proteins in vitro or in vivo. These systems have been tested in living cells. Thus, tmFRET can be applied to proteins in a living cell environment to map the conformational dynamics of proteins in vivo at the angstrom scale. Along with these studies of protein structure we have been designing and producing a new type of fluorescence protein. These proteins are based on the structure of the green fluorescent proteins (FPs). In these studies we engineered transition metal ion binding sites onto the barrel of the protein. These new metal-binding FPs still retains their bright fluorescent colors. In these new proteins, however, the binding of colored transition metal ions such as copper, cobalt, or nickel causes rapid and robust quenching of fluorescence. We tested these new probes in vitro and in cultured mammalian cells. These new probes provide a robust and tunable metal sensitive fluorescent protein that can be used for transition metal ion sensing applications or as multi-color tunable probes for cell biology.